The long-term goal of this research project is to understand the cellular, morphological and biochemical events which occur during the transdifferentiation of pigmented iris epithelial cells (IECs) from the dorsal iris of the adult newt eye Notophthalmus viridescens into lens fibers during lens regeneration. The increasing knowledge that growth factors act as mitogens on a variety of cell types and that their effect is mediated by extracellular matrix interactions and second messengers has evoked interest in studies dealing with the effect of such factors on regenerating systems. Experiments will be conducted both in vivo and in vitro. We will emphasize analysis of the dedifferentiation and redifferentiation phases of the regenerative process. This project will have the following specific objectives: (1) to determine the distribution of FGFs (FGF-1 and FGF-2), IGF-1 and TGF- beta and their receptors, using immunocytochemical techniques, during IEC transdifferentiation; (2) to examine the effects of the FGF family (FGF-1 and FGF-2) of growth factors, IGF-1 and TGF-B on IEC outgrowth, migration, proliferation and differentiation in vitro, and their possible interactions during the transdifferentiation of IECs, (3) to study gene expression of FGF-1, FGF-2 and their receptors during the transdifferentiation of IECs; and, (4) to determine growth factor requirements that promote both maintenance of IECs differentiated state and their transdifferentiation into lens cells in serum-free medium. In this project efforts will be made to obtain basic information about the control mechanisms of the process of cell dedifferentiation with the expectation of applying the ideas obtained to the dedifferentiative process which occurs during carcinogenesis. This research project will continue to provide students with the opportunity to learn different techniques, to involve them in the main scientific activity that is research, and to motivate them to pursue careers in different areas of biomedical research.